Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice

Christy M. Kelley, Brian E. Powers, Ramon Velazquez, Jessica A. Ash, Stephen D. Ginsberg, Barbara J. Strupp, Elliott J. Mufson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer's disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. Although DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3-7.5 months of age. Ts65Dn dams were maintained on a choline-supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring post weaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, and brains were sectioned and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75NTR). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn-unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21.

Original languageEnglish (US)
Pages (from-to)1390-1410
Number of pages21
JournalJournal of Comparative Neurology
Volume522
Issue number6
DOIs
StatePublished - Apr 15 2014
Externally publishedYes

Fingerprint

Cholinergic Neurons
Choline
Cholinergic Agents
Down Syndrome
Young Adult
Mothers
Diet
Choline O-Acetyltransferase
Weaning
Nerve Growth Factor Receptor
Basal Forebrain
Intellectual Disability
Alzheimer Disease
Genotype
Food
Pregnancy
Brain
Therapeutics

Keywords

  • Choline acetyltransferase
  • Diagonal band
  • Down syndrome
  • Medial septum
  • Nucleus basalis
  • P75 neurotrophin receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice. / Kelley, Christy M.; Powers, Brian E.; Velazquez, Ramon; Ash, Jessica A.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

In: Journal of Comparative Neurology, Vol. 522, No. 6, 15.04.2014, p. 1390-1410.

Research output: Contribution to journalArticle

Kelley, Christy M. ; Powers, Brian E. ; Velazquez, Ramon ; Ash, Jessica A. ; Ginsberg, Stephen D. ; Strupp, Barbara J. ; Mufson, Elliott J. / Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice. In: Journal of Comparative Neurology. 2014 ; Vol. 522, No. 6. pp. 1390-1410.
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abstract = "Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer's disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. Although DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3-7.5 months of age. Ts65Dn dams were maintained on a choline-supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring post weaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, and brains were sectioned and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75NTR). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn-unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21.",
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AU - Ginsberg, Stephen D.

AU - Strupp, Barbara J.

AU - Mufson, Elliott J.

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